Endocrine Oncology最新文献

SDHA secondary findings in germline testing: counseling and surveillance considerations 种系检测中的 SDHA 次要发现：咨询和监测注意事项

Endocrine Oncology Pub Date : 2024-04-01 DOI: 10.1530/eo-23-0043

Catherine Skefos, Pamela L Brock, Erica L Blouch, Samantha Greenberg

引用次数: 0

How to design a theranostic trial? 如何设计治疗试验？

Endocrine Oncology Pub Date : 2024-04-01 DOI: 10.1530/eo-23-0045

D. Siripongsatian, Quido G de Lussanet de la Sablonière, F. A. Verburg, T. Brabander

{"title":"How to design a theranostic trial?","authors":"D. Siripongsatian, Quido G de Lussanet de la Sablonière, F. A. Verburg, T. Brabander","doi":"10.1530/eo-23-0045","DOIUrl":"https://doi.org/10.1530/eo-23-0045","url":null,"abstract":"The field of nuclear theranostic clinical trials is continuously expanding as an increasing number of novel agents and treatment combinations are explored for treating advanced and metastatic cancers. Moving from ‘bench-to-bedside’ is oftentimes a complex and lengthy process. The objective of this overview is to explore the basic elements involved in designing clinical trials with a special focus on theranostics in nuclear medicine. The 'bench-to-bedside' journey involves translating basic scientific research into patient-effective treatments. Preclinical studies, a crucial initial step, are a complex process encompassing in vitro experiments, in vivo studies, and animal models to explore hypotheses in humans. Clinical trials follow, with predefined phases assessing safety, effectiveness, and comparisons to existing treatments. This process demands investments in data management, statistics, Good Clinical Practice (GCP) accreditations, and collaborative efforts for funding and sustainable pricing. Theranostics, merging diagnostics and personalized treatment, is at the forefront. Continuous efforts to enhance existing agents involve reducing adverse effects, exploring new indications, and incorporating advanced imaging modalities. Radionuclide therapy, unique with non-uniform distribution and complex radiobiology, plays a distinct role. This article explores trends and challenges in each clinical trial phase in light of the emerging field of theranostics in nuclear medicine, emphasizing meticulous trial design, dosimetry optimization, and the necessity of collaborative stakeholder efforts for successful implementation.","PeriodicalId":508879,"journal":{"name":"Endocrine Oncology","volume":"266 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140767512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mönckeberg sclerosis in patients with thyroid papillary carcinoma 甲状腺乳头状癌患者的门克伯格硬化症

Endocrine Oncology Pub Date : 2024-04-01 DOI: 10.1530/eo-23-0047

V. Venetsanaki, Eleana Zisimopoulou, Chrysanthi Zouli, M. Boudina, Konstantinos Gkiouras, P. Xirou, Aimilia Fotiadou, M. Stamati, E. Argyropoulou, Alexandra Chrisoulidou

{"title":"Mönckeberg sclerosis in patients with thyroid papillary carcinoma","authors":"V. Venetsanaki, Eleana Zisimopoulou, Chrysanthi Zouli, M. Boudina, Konstantinos Gkiouras, P. Xirou, Aimilia Fotiadou, M. Stamati, E. Argyropoulou, Alexandra Chrisoulidou","doi":"10.1530/eo-23-0047","DOIUrl":"https://doi.org/10.1530/eo-23-0047","url":null,"abstract":"Background: Mönckeberg sclerosis is a form of calcification of the tunica media of small and medium size arteries. It occurs more often in the peripheral arteries of the lower limbs and it has been associated with diabetes and renal disease. Although there are a few reports of Mönckeberg sclerosis in thyroid vessels, there are no data regarding its significance in thyroid disease.\u0000\u0000Objective: To investigate the possible prognostic value of Mönckeberg sclerosis in thyroid vessels of patients with diagnosed thyroid cancer.\u0000\u0000Methods: We retrospectively studied patients with papillary thyroid cancer treated at the Theagenio Hospital of Thessaloniki from 2005 to 2021. The patients were divided in two groups based on the presence, or not, of histopathological findings of Mönckeberg sclerosis in the thyroid vessels-along with papillary thyroid cancer. Patient characteristics, histopathological details, personal history of thyroid disease and metabolic parameters were compared between the two groups.\u0000\u0000Results: Thirty-three patients with papillary thyroid carcinoma and Mönckeberg sclerosis were identified and matched to thirty-three controls with papillary thyroid cancer, without evidence of Mönckeberg sclerosis. The metabolic profile of patients with Mönckeberg sclerosis was not significantly different from those who did not have Mönckeberg sclerosis. Moreover, the comparison between the two groups did not reveal any remarkable differences in terms of the aggressiveness of the disease.\u0000\u0000Conclusions: The presence of Mönckeberg sclerosis does not seem to impact on histological characteristics of patients with papillary thyroid cancer.","PeriodicalId":508879,"journal":{"name":"Endocrine Oncology","volume":"32 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140796700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MDM2 regulates the stability of AR, AR-V7, and TM4SF3 proteins in prostate cancer MDM2 调控前列腺癌中 AR、AR-V7 和 TM4SF3 蛋白的稳定性

Endocrine Oncology Pub Date : 2024-01-01 DOI: 10.1530/eo-23-0017

P. Khatiwada, Ujjwal Rimal, Zhengyang Han, L. Shemshedini

{"title":"MDM2 regulates the stability of AR, AR-V7, and TM4SF3 proteins in prostate cancer","authors":"P. Khatiwada, Ujjwal Rimal, Zhengyang Han, L. Shemshedini","doi":"10.1530/eo-23-0017","DOIUrl":"https://doi.org/10.1530/eo-23-0017","url":null,"abstract":"Androgen Receptor (AR) and its constitutively active splice variant AR Variant 7 (AR-V7) regulate genes essential for the development and progression of prostate cancer. Degradation of AR and AR-V7 by ubiquitination proteasomal pathway is important for the regulation of both their protein stability. Our published results demonstrated that interaction of TM4SF3 with either AR or AR-V7 leads to mutual stabilization due to reduction in their ubiquitination and proteasomal degradation. These results led us to search for a common E3 ligase for AR, AR-V7, and TM4SF3. Depletion by siRNA of several E3 ligases identified MDM2 as the common E3 ligase. MDM2 inhibition by siRNA depletion or using a pharmacological inhibitor (MDM2i) of its E3 ligase activity led to elevated levels of endogenous AR, AR-V7, and TM4SF3 in prostate cancer cells. MDM2 knockdown in PC-3 cells, which do not express AR, also increased TM4SF3, demonstrating that MDM2 affects the TM4SF3 protein independent of AR. We further demonstrate that MDM2i treatment reduced the ubiquitination of AR and TM4SF3, suggesting that MDM2 can induce the ubiquitination of these proteins. Increased AR and AR-V7 protein levels induced by MDM2i treatment resulted in the expected increased expression of AR-regulated genes and enhanced proliferation and migration of both LNCaP and Enzalutamide-resistant CWR-22Rv1 prostate cancer cells. Thus, our study expands the known roles of MDM2 in prostate cancer to include its potential involvement in the important mutual stabilization that TM4SF3 exhibits when interacting with either AR or AR-V7.","PeriodicalId":508879,"journal":{"name":"Endocrine Oncology","volume":"88 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139635281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The GLP-1 receptor is expressed in vivo by human metastatic prostate cancer 人转移性前列腺癌在体内表达 GLP-1 受体

Endocrine Oncology Pub Date : 2023-12-01 DOI: 10.1530/eo-23-0015

Mark Stein, Victor Kalff, Scott Williams, Declan G. Murphy, Peter G Colman, M. Hofman

{"title":"The GLP-1 receptor is expressed in vivo by human metastatic prostate cancer","authors":"Mark Stein, Victor Kalff, Scott Williams, Declan G. Murphy, Peter G Colman, M. Hofman","doi":"10.1530/eo-23-0015","DOIUrl":"https://doi.org/10.1530/eo-23-0015","url":null,"abstract":"OBJECTIVES: The glucagon-like peptide 1 (GLP-1) receptor agonist, Liraglutide, reduces human prostate cancer incidence and similar GLP-1 receptor agonists reduce in vitro proliferation and in vivo growth of prostate cancer cell lines. Primary human prostate cancer expresses the GLP-1 receptor (GLP-1R) in vitro. Cancer evolves with stage and whether advanced stage human prostate cancer expresses GLP-1R is unknown. We hypothesised and aimed to prove, that human metastatic castrate resistant prostate cancer (mCRPC) expresses the GLP-1R in vivo. We hypothesised mCRPC would thus be detectable by positron emission tomography/computed tomography (PET/CT) using radiotracer bound to a GLP-1R ligand, as in Exendin PET/CT. DESIGN AND METHODS: Men with mCRPC, with more than one prostate specific membrane antigen (PSMA)-avid lesion on PET/CT scanning (pathognomic in that setting for prostate cancer lesions), were approached to undergo PET/CT with Gallium68-Dota-Exendin-4. We documented PET/CT PSMA-avid lesions which were also PET/CT Exendin-avid as evidence of in vivo GLP-1R expression. RESULTS: Of 24 men referred, three did not meet inclusion criteria. Seventeen declined, largely because the study offered them no therapeutic benefit. Of four men imaged, three had no Exendin-avid lesions, one had six osseous PSMA-avid lesions, three of which were also Exendin-avid. CONCLUSIONS: We demonstrated in vivo GLP-1R expression by human mCPRC, detecting PET/CT lesions avid for both PSMA and Exendin, in one of four participants. GLP-1R expression may thus occur even in advanced stage prostate cancer. Our data contribute to growing evidence supporting the testing of GLP-1 receptor agonists for therapeutic benefit in prostate cancer.","PeriodicalId":508879,"journal":{"name":"Endocrine Oncology","volume":"12 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139196446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0